The overall objective of this project is a better understanding of the regulation of pulmonary ventilation. Specific goals are to: 1) determine if ventilatory acclimatization to chronic hypoxia (VACH) can be induced by stimulation of the peripheral chemoreceptors in the absence of cerebral hypoxia; 2) determine if venous CO2 loading plays a role in control of respiration, particularly during the hyperpnea of exercise, and 3) more clearly elucidate the role of peripheral chemoreceptor and potential central nervous system dopamine receptors in regulation of respiration. In part 1 the carotid body of awake goats will be vascularly isolated from the normoxic cerebral circulation and perfused by hypoxic blood to determine if this will elicit VACH. In part 2 we will vary the venous CO2 level in awake ponies by a extracorporeal circuit in order to determine if isocapnic hyperpnea can be elicited by elevated venous CO2. In part 3 ventilatory control studies including isocapnic hypoxia and hypercapnia will be carried out in awake goats before and after pharmacologic inhibition of peripheral chemoreceptor and CNS dopamine receptors. Similar studies will be carried out before and after peripheral chemoreceptor denervation to determine if CNS dopamine receptors are important in respiratory regulation. Apomorphine will be used as the agonist of CNS dopamine receptors. Supersensitivity of dopamine receptors will be induced by long-term administration of haloperidol to awake goats. We will determine if this modifies ventilatory responses to physiologic stimuli.